Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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    Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: An observational, prospective, cohort study
    (Wiley-Blackwell, 2017) Perera, D.M.P.; Coombes, J.A.; Shanika, L.G.T.; Dawson, A.; Lynch, C.; Mohamed, F.; Kalupahana, N.; de Silva, H.A.; Jayamanne, S.F.; Peters, N.B.; Myers, B.; Coombes, I.D.
    BACKGROUND: Quality use of medicines (QUM) has been identified as a priority in Sri Lanka. Aim: To identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital. METHODS: An observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre-admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre- and post-admission medication regimens were recorded. Drug-related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital. RESULTS: The 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge. CONCLUSION: Significant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospitalbased healthcare system in Sri Lanka. © 2017 The Society of Hospital Pharmacists of Australia.
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    Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning
    (Elsevier, 2016) Mohamed, F.; Endre, Z.H.; Pickering, J.W.; Jayamanne, S.; Palangasinghe, C.; Shahmy, S.; Chathuranga, U.; Wijerathne, T.; Shihana, F.; Gawarammana, I.; Buckley, N.A.
    Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood samples were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN ≥ 2 died. Increased sCr at 8 and 16 hours predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1); most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8 hours in patients who developed AKIN ≥ 2. Maximum 8 and 16 hour concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN ≥ 2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24 hours by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials.
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    High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention
    (Informa Healthcare, 2016) Lamb, T.; Selvarajah, L.R.; Mohamed, F.; Jayamanne, S.; Gawarammana, I.; Mostafa, A.; Buckley, N.A.; Roberts, M.S.; Eddleston, M.
    BACKGROUND: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.
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